DNA Repair Disorders

Abstract

Some human diseases are characterized by defects in the cellular machinery for either monitoring and eliciting an appropriate
response to the presence of DNA damage or in the actual process of removing (repairing) or tolerating the damage via some
type of DNA transaction. Many of the known disorders lead to a predisposition for developing cancer.

DNA repair and damage‐monitoring pathways. The presence of DNA damage in the genome of a cell is monitored by DNA‐damage sensors
which, in turn, send appropriate signals to the cellular response machinery including DNA‐repair pathways and cell cycle checkpoint
control systems (other responses). DNA repair is thought be conducted in transcribed (gene expression) regions by the transcription‐coupled
repair (TCR) system or in other genomic regions by the global genome repair (GGR) system. Components of specific DNA‐repair pathways that may participate in TCR or GGR are base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR). In some cases, DNA damage is handled by damage‐tolerance pathways such as translesion synthesis (TLS) and recombination
(REC).

Figure 2.

Biological endpoints of unrepaired DNA damage. The consequences of inability to mount an appropriate response to the presence
of DNA damage leads to a number of potentially deleterious consequences.